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Peer-reviewedCC BY 4.0Development (Cambridge, England)

Postnatal heart development is coordinated by multi-lineage Wnt and BMP signaling

  • Hui An1,2
  • Hao Hu1
  • Saijing Chen2
  • Tingting Chen1
  • Yafei Hu1
  • Tongtong Yu1
  • Anlan Wang1
  • Shengwei Jin1
  • Ming Li1,2
  1. 1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Key Laboratory of Pediatric Anesthesiology (Wenzhou Medical University), Ministry of Education; Key Laboratory of Precision Anesthesiology of Zhejiang Province, Wenzhou Medical University, Zhejiang 325027, China
  2. 2School of Basic Medical Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
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Abstract

Early postnatal heart growth requires a transition from cardiomyocyte proliferation to enlargement and binucleation. Using morphometric, transcriptomic, signaling and single-cell analyses in neonatal mice, we show that this transition occurs predominantly between postnatal days 3.5 and 4.5 (P3.5-P4.5), accompanied by declining β-catenin abundance and increased SMAD1/5/9 phosphorylation. Pharmacological disruption of β-catenin/CBP signaling or Ctnnb1 knockdown promotes cardiomyocyte enlargement, whereas β-catenin stabilization by CHIR-99021 enhances cell-cycle activity and estimated ventricular cardiomyocyte number while limiting enlargement. Transcriptomic analysis reveals a Sox2/Zic1/Olig2 module enriched in early neural/glial cells, suggesting the onset of postnatal cardiac nervous system development. Wnt pathway components are active in endothelial, mesenchymal and neural populations during the early postnatal window, whereas BMP signaling peaks in cardiomyocytes at P6. These findings reveal a multi-lineage interplay between Wnt and BMP signaling that balances cardiomyocyte number expansion versus enlargement during early postnatal heart development.

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Cite

BibTeXRIS
BibTeX
@article{an2026postnatal,
  title = {{Postnatal heart development is coordinated by multi-lineage Wnt and BMP signaling}},
  author = {Hui An and Hao Hu and Saijing Chen and Tingting Chen and Yafei Hu and Tongtong Yu and Anlan Wang and Shengwei Jin and Ming Li},
  journal = {Development (Cambridge, England)},
  year = {2026},
  month = oct,
  doi = {10.1242/dev.205448},
  url = {https://doi.org/10.1242/dev.205448},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Postnatal heart development is coordinated by multi-lineage Wnt and BMP signaling
AU  - Hui An
AU  - Hao Hu
AU  - Saijing Chen
AU  - Tingting Chen
AU  - Yafei Hu
AU  - Tongtong Yu
AU  - Anlan Wang
AU  - Shengwei Jin
AU  - Ming Li
PY  - 2026
DA  - 2026/10/06
JO  - Development (Cambridge, England)
DO  - 10.1242/dev.205448
UR  - https://doi.org/10.1242/dev.205448
AB  - Early postnatal heart growth requires a transition from cardiomyocyte proliferation to enlargement and binucleation. Using morphometric, transcriptomic, signaling and single-cell analyses in neonatal mice, we show that this transition occurs predominantly between postnatal days 3.5 and 4.5 (P3.5-P4.5), accompanied by declining β-catenin abundance and increased SMAD1/5/9 phosphorylation. Pharmacological disruption of β-catenin/CBP signaling or Ctnnb1 knockdown promotes cardiomyocyte enlargement, whereas β-catenin stabilization by CHIR-99021 enhances cell-cycle activity and estimated ventricular cardiomyocyte number while limiting enlargement. Transcriptomic analysis reveals a Sox2/Zic1/Olig2 module enriched in early neural/glial cells, suggesting the onset of postnatal cardiac nervous system development. Wnt pathway components are active in endothelial, mesenchymal and neural populations during the early postnatal window, whereas BMP signaling peaks in cardiomyocytes at P6. These findings reveal a multi-lineage interplay between Wnt and BMP signaling that balances cardiomyocyte number expansion versus enlargement during early postnatal heart development.
SN  - 0950-1991
SN  - 1477-9129
ER  -